tbuckley/cabot-search huggingface dataset:
Early vs Standard Approach to Tracheostomy and Functional Outcome Among Patients With Severe Stroke Receiving Mechanical Ventilation
Authors: Guanggang Li, Feihu Zhou
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Deep Venous Thrombosis
Authors: Lisa Duffett
Journal: Annals of Internal Medicine (2022)

Venous thromboembolism (VTE) is the third most common cardiovascular disorder, affecting up to 5% of the population. VTE commonly manifests as lower-extremity deep venous thrombosis (DVT) or pulmonary embolism. Half of these events are associated with a transient risk factor and may be preventable with prophylaxis. Direct oral anticoagulants are effective and safe and carry a lower risk for bleeding than vitamin K antagonists. Many patients with VTE will have a chronic disease requiring long-term anticoagulation. Postthrombotic syndrome affects 25% to 40% of patients with DVT and significantly impacts function and quality of life.
Selective targeting of GARP-LTGFβ axis in the tumor microenvironment augments PD-1 blockade via enhancing CD8<sup>+</sup>T cell antitumor immunity
Authors: Anqi Li, Yuzhou Chang, No-Joon Song, Xingjun Wu, Dongjun Chung, Brian P Riesenberg, Maria Velegraki, Giuseppe D Giuliani, Komal Das, Tamio Okimoto, Hyunwoo Kwon, Karthik B Chakravarthy, Chelsea Bolyard, Yi Wang, Kai He, Margaret Gatti-Mays, Jayajit Das, Yiping Yang, Daniel T Gewirth, Qin Ma, David Carbone, Zihai Li
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Immune checkpoint blockade (ICB) has revolutionized cancer immunotherapy. However, most patients with cancer fail to respond clinically. One potential reason is the accumulation of immunosuppressive transforming growth factor β (TGFβ) in the tumor microenvironment (TME). TGFβ drives cancer immune evasion in part by inducing regulatory T cells (Tregs) and limiting CD8 + T cell function. Glycoprotein-A repetitions predominant (GARP) is a cell surface docking receptor for activating latent TGFβ1, TGFβ2 and TGFβ3, with its expression restricted predominantly to effector Tregs, cancer cells, and platelets. Methods We investigated the role of GARP in human patients with cancer by analyzing existing large databases. In addition, we generated and humanized an anti-GARP monoclonal antibody and evaluated its antitumor efficacy and underlying mechanisms of action in murine models of cancer. Results We demonstrate that GARP overexpression in human cancers correlates with a tolerogenic TME and poor clinical response to ICB, suggesting GARP blockade may improve cancer immunotherapy. We report on a unique anti-human GARP antibody (named PIIO-1) that specifically binds the ligand-interacting domain of all latent TGFβ isoforms. PIIO-1 lacks recognition of GARP-TGFβ complex on platelets. Using human LRRC32 (encoding GARP) knock-in mice, we find that PIIO-1 does not cause thrombocytopenia; is preferentially distributed in the TME; and exhibits therapeutic efficacy against GARP + and GARP - cancers, alone or in combination with anti-PD-1 antibody. Mechanistically, PIIO-1 treatment reduces canonical TGFβ signaling in tumor-infiltrating immune cells, prevents T cell exhaustion, and enhances CD8 + T cell migration into the TME in a C-X-C motif chemokine receptor 3 (CXCR3)-dependent manner. Conclusion GARP contributes to multiple aspects of immune resistance in cancer. Anti-human GARP antibody PIIO-1 is an efficacious and safe strategy to block GARP-mediated LTGFβ activation, enhance CD8 + T cell trafficking and functionality in the tumor, and overcome primary resistance to anti-PD-1 ICB. PIIO-1 therefore warrants clinical development as a novel cancer immunotherapeutic.
Controlled therapeutic delivery of CO from carbon monoxide-releasing molecules (CORMs)
Authors: Ho-Ik Choi, Alam Zeb, Min-Su Kim, Isra Rana, Namrah Khan, Omer Salman Qureshi, Chang-Wan Lim, Jeong-Sook Park, Zhonggao Gao, Han-Joo Maeng, Jin-Ki Kim
Journal: Journal of Controlled Release (2022)
Automated, scaled, transposon-based production of CAR T cells
Authors: Dominik Lock, Razieh Monjezi, Caroline Brandes, Stephan Bates, Simon Lennartz, Karin Teppert, Leon Gehrke, Rafailla Karasakalidou-Seidt, Teodora Lukic, Marco Schmeer, Martin Schleef, Niels Werchau, Matthias Eyrich, Mario Assenmacher, Andrew Kaiser, Sabrina Prommersberger, Thomas Schaser, Michael Hudecek
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background There is an increasing demand for chimeric antigen receptor (CAR) T cell products from patients and care givers. Here, we established an automated manufacturing process for CAR T cells on the CliniMACS Prodigy platform that is scaled to provide therapeutic doses and achieves gene-transfer with virus-free Sleeping Beauty (SB) transposition. Methods We used an advanced CliniMACS Prodigy that is connected to an electroporator unit and performed a series of small-scale development and large-scale confirmation runs with primary human T cells. Transposition was accomplished with minicircle (MC) DNA-encoded SB100X transposase and pT2 transposon encoding a CD19 CAR. Results We defined a bi-pulse electroporation shock with bi-directional and unidirectional electric field, respectively, that permitted efficient MC insertion and maintained a high frequency of viable T cells. In three large scale runs, 2E8 T cells were enriched from leukapheresis product, activated, gene-engineered and expanded to yield up to 3.5E9 total T cells/1.4E9 CAR-modified T cells within 12 days (CAR-modified T cells: 28.8%±12.3%). The resulting cell product contained highly pure T cells (97.3±1.6%) with balanced CD4/CD8 ratio and a high frequency of T cells with central memory phenotype (87.5%±10.4%). The transposon copy number was 7.0, 9.4 and 6.8 in runs #1–3, respectively, and gene analyses showed a balanced expression of activation/exhaustion markers. The CD19 CAR T cell product conferred potent anti-lymphoma reactivity in pre-clinical models. Notably, the operator hands-on-time was substantially reduced compared with conventional non-automated CAR T cell manufacturing campaigns. Conclusions We report on the first automated transposon-based manufacturing process for CAR T cells that is ready for formal validation and use in clinical manufacturing campaigns. This process and platform have the potential to facilitate access of patients to CAR T cell therapy and to accelerate scaled, multiplexed manufacturing both in the academic and industry setting.
Effective treatment of low-risk acute GVHD with itacitinib monotherapy
Authors: Aaron Etra, Alexandra Capellini, Amin Alousi, Monzr M. Al Malki, Hannah Choe, Zachariah DeFilipp, William J. Hogan, Carrie L. Kitko, Francis Ayuk, Janna Baez, Isha Gandhi, Stelios Kasikis, Sigrun Gleich, Elizabeth Hexner, Matthias Hoepting, Urvi Kapoor, Steven Kowalyk, Deukwoo Kwon, Amelia Langston, Marco Mielcarek, George Morales, Umut Özbek, Muna Qayed, Ran Reshef, Wolf Rösler, Nikolaos Spyrou, Rachel Young, Yi-Bin Chen, James L. M. Ferrara, John E. Levine
Journal: Blood (2022)
Distinct cellular dynamics associated with response to CAR-T therapy for refractory B cell lymphoma
Authors: Nicholas J. Haradhvala, Mark B. Leick, Katie Maurer, Satyen H. Gohil, Rebecca C. Larson, Ning Yao, Kathleen M. E. Gallagher, Katelin Katsis, Matthew J. Frigault, Jackson Southard, Shuqiang Li, Michael C. Kann, Harrison Silva, Max Jan, Kahn Rhrissorrakrai, Filippo Utro, Chaya Levovitz, Raquel A. Jacobs, Kara Slowik, Brian P. Danysh, Kenneth J. Livak, Laxmi Parida, Judith Ferry, Caron Jacobson, Catherine J. Wu, Gad Getz, Marcela V. Maus
Journal: Nature Medicine (2022)
Loss of MLL Induces Epigenetic Dysregulation of Rasgrf1 to Attenuate Kras-Driven Lung Tumorigenesis
Authors: Ling-Yu Zhu, Jun-Bo Yuan, Li Zhang, Chun-Xiao He, Xiao Lin, Bin Xu, Guang-Hui Jin
Journal: Cancer Research (2022)

Abstract Menin is necessary for the formation of the menin/mixed lineage leukemia (MLL) complex and is recruited directly to chromatin. Menin is an important tumor suppressor in several cancer types, including lung cancer. Here, we investigated the role of MLL in menin-regulated lung tumorigenesis. Ablation of MLL suppressed KrasG12D-induced lung tumorigenesis in a genetically engineered mouse model. MLL deficiency decreased histone H3 lysine 4 trimethylation (H3K4me3) and subsequently suppressed expression of the Ras protein-specific guanine nucleotide-releasing factor 1 (Rasgrf1) gene. Rasgrf1 was essential for the GTP-bound active state of Kras and the activation of Kras downstream pathways as well as their cancer-promoting activities. MI-3, a small-molecule inhibitor targeting MLL, specifically inhibited the growth of Kras-mutated lung cancer cells in vitro and in vivo with minimal effect on wild-type Kras lung cancer growth. Together, these results demonstrate a novel tumor promoter function of MLL in mutant Kras-induced lung tumorigenesis and further indicate that specific blockade of the MLL-Rasgrf1 pathway may be a potential therapeutic strategy for the treatment of tumors containing Kras mutations. Significance: Activation of mutant Kras is dependent on MLL-mediated epigenetic regulation of Rasgrf1, conferring sensitivity to small-molecule inhibition of MLL in Kras-driven lung cancer.
Obesity Is Associated with Attenuated Tissue Immunity in COVID-19
Authors: Shuang A. Guo, Georgina S. Bowyer, John R. Ferdinand, Mailis Maes, Zewen K. Tuong, Eleanor Gillman, Mingfeng Liao, Rik G. H. Lindeboom, Masahiro Yoshida, Kaylee Worlock, Hudaa Gopee, Emily Stephenson, Catherine A. Gao, Paul A. Lyons, Kenneth G. C. Smith, Muzlifah Haniffa, Kerstin B. Meyer, Marko Z. Nikolić, Zheng Zhang, Richard G. Wunderink, Alexander V. Misharin, Gordon Dougan, Vilas Navapurkar, Sarah A. Teichmann, Andrew Conway Morris, Menna R. Clatworthy
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Obesity affects 40% of U.S. adults, is associated with a proinflammatory state, and presents a significant risk factor for the development of severe coronavirus disease (COVID-19). To date, there is limited information on how obesity might affect immune cell responses in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
Medicare’s Bundled Payment Models—Reply
Authors: Karen E. Joynt Maddox, Sukruth A. Shashikumar, Andrew M. Ryan
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Early vs Standard Approach to Tracheostomy and Functional Outcome Among Patients With Severe Stroke Receiving Mechanical Ventilation—Reply
Authors: Julian Bösel, Silvia Schönenberger, David B. Seder
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
EVI1 drives leukemogenesis through aberrant ERG activation
Authors: Johannes Schmoellerl, Inês A.M. Barbosa, Martina Minnich, Florian Andersch, Leonie Smeenk, Marije Havermans, Thomas Eder, Tobias Neumann, Julian Jude, Michaela Fellner, Anja Ebert, Monika Steininger, Ruud Delwel, Florian Grebien, Johannes Zuber
Journal: Blood (2022)
Clonal hematopoiesis of indeterminate potential and risk of death from COVID-19
Authors: Peter G. Miller, Geoffrey G. Fell, Brody H. Foy, Allison K. Scherer, Christopher J. Gibson, Adam S. Sperling, Bala B. Burugula, Tetsushi Nakao, Md M. Uddin, Hailey Warren, Lynn Bry, Olga Pozdnyakova, Matthew J. Frigault, Alex G. Bick, Donna Neuberg, John M. Higgins, Michael K. Mansour, Pradeep Natarajan, Annette S. Kim, Jacob O. Kitzman, Benjamin L. Ebert
Journal: Blood (2022)
R-spondin/YAP axis promotes gastric oxyntic gland regeneration and Helicobacter pylori–associated metaplasia in mice
Authors: Anne-Sophie Fischer, Stefanie Müllerke, Alexander Arnold, Julian Heuberger, Hilmar Berger, Manqiang Lin, Hans-Joachim Mollenkopf, Jonas Wizenty, David Horst, Frank Tacke, Michael Sigal
Journal: Journal of Clinical Investigation (2022)

The stomach corpus epithelium is organized into anatomical units that consist of glands and pits. Mechanisms that control the cellular organization of corpus glands and enable their recovery upon injury are not well understood. R-spondin 3 (RSPO3) is a WNT-signaling enhancer that regulates stem cell behavior in different organs. Here, we investigated the function of RSPO3 in the corpus during homeostasis, upon chief and/or parietal cell loss, and during chronic Helicobacter pylori infection. Using organoid culture and conditional mouse models, we demonstrate that RSPO3 is a critical driver of secretory cell differentiation in the corpus gland toward parietal and chief cells, while its absence promoted pit cell differentiation. Acute loss of chief and parietal cells induced by high dose tamoxifen — or merely the depletion of LGR5+ chief cells — caused an upregulation of RSPO3 expression, which was required for the initiation of a coordinated regenerative response via the activation of yes-associated protein (YAP) signaling. This response enabled a rapid recovery of the injured secretory gland cells. However, in the context of chronic H. pylori infection, the R-spondin–driven regeneration was maintained long term, promoting severe glandular hyperproliferation and the development of premalignant metaplasia.
Modeling Optimal Clinical Thresholds for Elective Abdominal Hernia Repair in Patients With Cirrhosis
Authors: Nadim Mahmud, David S. Goldberg, Samir Abu-Gazala, James D. Lewis, David E. Kaplan
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Patients with cirrhosis have increased risk of postoperative mortality. Several models have been developed to estimate this risk; however, current risk estimation scores cannot compare surgical risk with the risk of not operating. <h3>Objective</h3> To identify clinical optimal thresholds to favor operative or nonoperative management for a common cirrhosis surgical scenario, the symptomatic abdominal hernia. <h3>Design, Setting, and Participants</h3> This was a Markov cohort decision analytical modeling study evaluating elective surgery vs nonoperative management for a symptomatic abdominal hernia in a patient with cirrhosis. Transition probabilities and utilities were derived from the literature and from data using an established cirrhosis cohort in the Veterans Health Administration. Participants included patients who were referred to a surgery clinic for a symptomatic abdominal hernia. Data were obtained from patients diagnosed with cirrhosis between January 1, 2008 and December 31, 2018. Data were analyzed from January 1 to May 1, 2022. <h3>Main Outcomes and Measures</h3> Expected quality-adjusted life-years (QALYs) were estimated for each pathway and iterated over baseline model for end-stage liver disease–sodium (MELD-Na) scores ranging from 6 to 25. Markov models were cycled over a 5-year time horizon. <h3>Results</h3> A total 2740 patients with cirrhosis (median [IQR] age, 62 [56-66] years; 2699 [98.5%] men) were referred to a surgery clinic for a symptomatic abdominal hernia; 1752 patients (63.9%) did not receive surgery. The median (IQR) follow-up was 42.1 (25.3-70.0) months. Using this cohort to estimate the mortality risk of operative and nonoperative pathways, an initial MELD-Na threshold of 21.3 points, below which surgery was associated with maximized QALYs was identified. Nonoperative management was associated with increased QALYs above this MELD-Na threshold. Although more patients experienced death with a surgical treatment decision across all initial MELD-Na values, this was counterbalanced by increased time spent in a resolved hernia state associated with increased utility. Model results were sensitive to the probability of hernia recurrence and hernia incarceration and utility decrement in the symptomatic hernia state. <h3>Conclusions and Relevance</h3> This decision analytical model study found that elective surgical treatment for a symptomatic abdominal hernia was favored even in the setting of relatively high MELD-Na scores. Patient symptoms, hernia-specific characteristics, and surgeon and center expertise may potentially impact the optimal strategy, emphasizing the importance of shared decision-making.
Significant Trends in Cancer Research
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Recommendations for Screening Children and Adolescents for Prediabetes and Type 2 Diabetes
Authors: Elvira Isganaitis, Lori Laffel
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Association of Perceived Lack of Paternal Support After Stillbirth With Maternal Postpartum Depression or Anxiety
Authors: Adam K. Lewkowitz, Tess E. K. Cersonsky, Uma M. Reddy, Robert L. Goldenberg, Donald J. Dudley, Robert M. Silver, Nina K. Ayala
Journal: JAMA Network Open (2022)

a The pertinent yes or no question on the survey was, "Please let me know if you found the father of the baby helpful or supportive [time point]."This question was asked 3 times to reference 3 different time points: before the stillbirth, immediately after diagnosis of stillbirth, and 2 months following stillbirth.b Nonadjusted odds ratio from univariate logistic regression.c Adjusted for maternal race and ethnicity, prepregnancy depression and anxiety, and substance use during pregnancy in multivariate logistic regression.Prepregnancy depression and anxiety and substance use during pregnancy were selfreported during a predelivery interview.
There Is No Magic Pill to Prevent Frailty—You Still Have to Eat Your Vegetables
Authors: Elizabeth Eckstrom, Bryanna De Lima
Journal: JAMA Network Open (2022)

Ariela R. Orkaby, MD, MPH; Rimma Dushkes, PhD; Rachel Ward, PhD; Luc Djousse, MD, ScD; Julie E. Buring, ScD; I-Min Lee, MBBS, ScD; Nancy R. Cook, ScD; Meryl S. LeBoff, MD; Olivia I. Okereke, MD, SM; Trisha Copeland, MS, RD; JoAnn E. Manson, MD, DrPH